TY  - THES
AU  - Cvijetić, Ilija
PY  - 2016
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=4755
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:15023/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48827407
UR  - http://nardus.mpn.gov.rs/123456789/7870
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2713
AB  - Rastuća otpornost bakterija prema dejstvu gotovo svih poznatih antibiotikazahteva pronalaženje novih hemijskih struktura koje efikasno deluju na multirezistentne(Multi-drug resistant, MDR) bakterije. Kao nastavak istraživanja antibakterijskeaktivnosti 4-aril-2,4-dioksobutanskih kiselina (arildiketokiselina, ADK) započetih ranijeu okviru naše istraživačke grupe, u okviru ove doktorske disertacije sintetisana je novaserija od dvadeset i jedne ADK (jedinjenja 1-21) i ispitana im je antibakterijskaaktivnost prema MDR sojevima bakterija. Jedinjenja sa voluminoznim alkilsupstituentima u orto-položaju fenilnog jezgra pokazala su se najaktivnijim premanorfloksacin-rezistentnom soju bakterije Staphylococcus aureus, a jedinjenje 12(4-(2,5-di-cikloheksilfenil)-2,4-dioksobutanska kiselina) je pokazalo 10-11 puta većuaktivnost prema istom soju bakterija od najaktivnijeg jedinjenja iz prethodno objavljeneserije ADK, kao i 10 puta veću aktivnost od norfloksacina. Narušavanjem strukturediketo dela molekula značajno se smanjuje antibakterijska aktivnost ADK...
AB  - Growing bacterial resistance toward almost all known antibiotics demands rapiddiscovery of the novel chemical entities active toward multidrug resistant (MDR)bacterial strains. As a continuation of research on antibacterial activity of 4-aryl-2,4-dioxobutanoic acids (ADK), synthesis and antibacterial activity of twenty one novelADKs (compounds 1-21) are reported in this thesis. Compounds bearing bulky alkylsubstituents in ortho-position on phenyl ring were the most active against norfloxacinresistantstrain of Staphylococcus aureus. Compound 12 was 10-11 times more potentthan the most potent ADK from previously published set of compounds, and also 10times more potent than norfloxacin tested against the same bacterial strain. Diketomoiety was proven to be essential for antibacterial activity of ADK...
PB  - Универзитет у Београду, Хемијски факултет
T2  - Универзитет у Београду
T1  - Hemijska i biološka karakterizacija novosintetisanih derivata 4-aril-2, 4-dioksobutanskih kiiselina i molekulsko modelovanje u cilju racionalizacije biološke aktivnosti i fizičko-hemijskih osobina
UR  - https://hdl.handle.net/21.15107/rcub_nardus_7870
ER  - 

@phdthesis{
author = "Cvijetić, Ilija",
year = "2016",
abstract = "Rastuća otpornost bakterija prema dejstvu gotovo svih poznatih antibiotikazahteva pronalaženje novih hemijskih struktura koje efikasno deluju na multirezistentne(Multi-drug resistant, MDR) bakterije. Kao nastavak istraživanja antibakterijskeaktivnosti 4-aril-2,4-dioksobutanskih kiselina (arildiketokiselina, ADK) započetih ranijeu okviru naše istraživačke grupe, u okviru ove doktorske disertacije sintetisana je novaserija od dvadeset i jedne ADK (jedinjenja 1-21) i ispitana im je antibakterijskaaktivnost prema MDR sojevima bakterija. Jedinjenja sa voluminoznim alkilsupstituentima u orto-položaju fenilnog jezgra pokazala su se najaktivnijim premanorfloksacin-rezistentnom soju bakterije Staphylococcus aureus, a jedinjenje 12(4-(2,5-di-cikloheksilfenil)-2,4-dioksobutanska kiselina) je pokazalo 10-11 puta većuaktivnost prema istom soju bakterija od najaktivnijeg jedinjenja iz prethodno objavljeneserije ADK, kao i 10 puta veću aktivnost od norfloksacina. Narušavanjem strukturediketo dela molekula značajno se smanjuje antibakterijska aktivnost ADK..., Growing bacterial resistance toward almost all known antibiotics demands rapiddiscovery of the novel chemical entities active toward multidrug resistant (MDR)bacterial strains. As a continuation of research on antibacterial activity of 4-aryl-2,4-dioxobutanoic acids (ADK), synthesis and antibacterial activity of twenty one novelADKs (compounds 1-21) are reported in this thesis. Compounds bearing bulky alkylsubstituents in ortho-position on phenyl ring were the most active against norfloxacinresistantstrain of Staphylococcus aureus. Compound 12 was 10-11 times more potentthan the most potent ADK from previously published set of compounds, and also 10times more potent than norfloxacin tested against the same bacterial strain. Diketomoiety was proven to be essential for antibacterial activity of ADK...",
publisher = "Универзитет у Београду, Хемијски факултет",
journal = "Универзитет у Београду",
title = "Hemijska i biološka karakterizacija novosintetisanih derivata 4-aril-2, 4-dioksobutanskih kiiselina i molekulsko modelovanje u cilju racionalizacije biološke aktivnosti i fizičko-hemijskih osobina",
url = "https://hdl.handle.net/21.15107/rcub_nardus_7870"
}

Cvijetić, I.. (2016). Hemijska i biološka karakterizacija novosintetisanih derivata 4-aril-2, 4-dioksobutanskih kiiselina i molekulsko modelovanje u cilju racionalizacije biološke aktivnosti i fizičko-hemijskih osobina. in Универзитет у Београду
Универзитет у Београду, Хемијски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_7870

Cvijetić I. Hemijska i biološka karakterizacija novosintetisanih derivata 4-aril-2, 4-dioksobutanskih kiiselina i molekulsko modelovanje u cilju racionalizacije biološke aktivnosti i fizičko-hemijskih osobina. in Универзитет у Београду. 2016;.
https://hdl.handle.net/21.15107/rcub_nardus_7870 .

Cvijetić, Ilija, "Hemijska i biološka karakterizacija novosintetisanih derivata 4-aril-2, 4-dioksobutanskih kiiselina i molekulsko modelovanje u cilju racionalizacije biološke aktivnosti i fizičko-hemijskih osobina" in Универзитет у Београду (2016),
https://hdl.handle.net/21.15107/rcub_nardus_7870 .

TY  - JOUR
AU  - Vitorović-Todorović, Maja D.
AU  - Koukoulitsa, Catherine
AU  - Juranić, Ivan O.
AU  - Mandić, Ljuba M.
AU  - Drakulić, Branko J.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1808
AB  - Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations
VL  - 81
SP  - 158
EP  - 175
DO  - 10.1016/j.ejmech.2014.05.008
ER  - 

@article{
author = "Vitorović-Todorović, Maja D. and Koukoulitsa, Catherine and Juranić, Ivan O. and Mandić, Ljuba M. and Drakulić, Branko J.",
year = "2014",
abstract = "Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations",
volume = "81",
pages = "158-175",
doi = "10.1016/j.ejmech.2014.05.008"
}

Vitorović-Todorović, M. D., Koukoulitsa, C., Juranić, I. O., Mandić, L. M.,& Drakulić, B. J.. (2014). Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 81, 158-175.
https://doi.org/10.1016/j.ejmech.2014.05.008

Vitorović-Todorović MD, Koukoulitsa C, Juranić IO, Mandić LM, Drakulić BJ. Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations. in European Journal of Medicinal Chemistry. 2014;81:158-175.
doi:10.1016/j.ejmech.2014.05.008 .

Vitorović-Todorović, Maja D., Koukoulitsa, Catherine, Juranić, Ivan O., Mandić, Ljuba M., Drakulić, Branko J., "Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE-ligand interactions by docking calculations and molecular dynamics simulations" in European Journal of Medicinal Chemistry, 81 (2014):158-175,
https://doi.org/10.1016/j.ejmech.2014.05.008 . .

TY  - JOUR
AU  - Cvijetić, Ilija
AU  - Vitorović-Todorović, Maja D.
AU  - Juranić, Ivan O.
AU  - Nakarada, Dura J.
AU  - Milosavljević, Milica D.
AU  - Drakulić, Branko J.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1816
AB  - Rates of the aza-Michael addition of piperidine and benzylamine to thirteen (E)-4-aryl-4-oxo-2-butenoic acid phenylamides (AACPs) are reported. Progress of the reaction was monitored by UV/Vis spectroscopy. The 2D NMR spectra confirmed regioselectivity of the reactions. Piperidine and benzylamine provide exclusively beta-adducts in respect to the aroyl keto group. Influence of the substituents of the aroyl phenyl ring of AACPs on the rate of the reaction was quantified by Hammett substituent constants, partial atomic charges, and the energies of frontier orbitals. Good correlations between second-order rate constants and the Hammett substituent constants were obtained (r = 0.98, piperidine; r = 0.94, benzylamine) for para-, and meta-, para-substituted derivatives. Best correlations were obtained with the energies of the lowest unoccupied molecular orbitals of compounds, derived from the MP2 level of theory. Calculated UV/Vis spectra of representative AACPs and their Michael adduct with piperidine and benzylamine are in fair agreement with experimentally obtained data.
PB  - Springer Wien, Wien
T2  - Monatshefte Fur Chemie
T1  - Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study
VL  - 145
IS  - 8
SP  - 1297
EP  - 1306
DO  - 10.1007/s00706-014-1223-8
ER  - 

@article{
author = "Cvijetić, Ilija and Vitorović-Todorović, Maja D. and Juranić, Ivan O. and Nakarada, Dura J. and Milosavljević, Milica D. and Drakulić, Branko J.",
year = "2014",
abstract = "Rates of the aza-Michael addition of piperidine and benzylamine to thirteen (E)-4-aryl-4-oxo-2-butenoic acid phenylamides (AACPs) are reported. Progress of the reaction was monitored by UV/Vis spectroscopy. The 2D NMR spectra confirmed regioselectivity of the reactions. Piperidine and benzylamine provide exclusively beta-adducts in respect to the aroyl keto group. Influence of the substituents of the aroyl phenyl ring of AACPs on the rate of the reaction was quantified by Hammett substituent constants, partial atomic charges, and the energies of frontier orbitals. Good correlations between second-order rate constants and the Hammett substituent constants were obtained (r = 0.98, piperidine; r = 0.94, benzylamine) for para-, and meta-, para-substituted derivatives. Best correlations were obtained with the energies of the lowest unoccupied molecular orbitals of compounds, derived from the MP2 level of theory. Calculated UV/Vis spectra of representative AACPs and their Michael adduct with piperidine and benzylamine are in fair agreement with experimentally obtained data.",
publisher = "Springer Wien, Wien",
journal = "Monatshefte Fur Chemie",
title = "Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study",
volume = "145",
number = "8",
pages = "1297-1306",
doi = "10.1007/s00706-014-1223-8"
}

Cvijetić, I., Vitorović-Todorović, M. D., Juranić, I. O., Nakarada, D. J., Milosavljević, M. D.,& Drakulić, B. J.. (2014). Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study. in Monatshefte Fur Chemie
Springer Wien, Wien., 145(8), 1297-1306.
https://doi.org/10.1007/s00706-014-1223-8

Cvijetić I, Vitorović-Todorović MD, Juranić IO, Nakarada DJ, Milosavljević MD, Drakulić BJ. Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study. in Monatshefte Fur Chemie. 2014;145(8):1297-1306.
doi:10.1007/s00706-014-1223-8 .

Cvijetić, Ilija, Vitorović-Todorović, Maja D., Juranić, Ivan O., Nakarada, Dura J., Milosavljević, Milica D., Drakulić, Branko J., "Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study" in Monatshefte Fur Chemie, 145, no. 8 (2014):1297-1306,
https://doi.org/10.1007/s00706-014-1223-8 . .

TY  - JOUR
AU  - Cvijetić, Ilija
AU  - Petrović, D.D.
AU  - Verbić, Tatjana
AU  - Juranić, Ivan O.
AU  - Drakulić, B.J.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/333
AB  - Interactions of 2-[(carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic acid (compound 1) and its mono-Me ester (compound 2) with the human serum albumin (HSA) have been studied by fluorescence spectroscopy. Comp. 1 exerts antiproliferative activity toward human tumor cells and significant selectivity (tumor vs. healthy cells) in vitro. Competitive binding study with warfarin and ibuprofen as binding site probes, revealed that one molecule of comp. 1 selectively binds to HSA Sudlow site I (warfarin site) with moderate binding constant (Kb = (2.8 ± 0.5) × 104 M-1 at 37 ± 1 °C), while comp. 2 binds to Sudlow site II (Kb = (3.2 ± 0.9) × 104 M-1 at 37 ± 1 °C). Fluorescence quenching at different temperatures was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. Energy resonance transfer between HSA and comp. 1 was examined according to Förster's non-radiative energy transfer theory. Distance of about 10 Å between ligand and Trp214 (HSA) was obtained. Docking studies confirmed HSA Sudlow site I as a preferable comp. 1 binding site, and Sudlow site II as comp. 2 binding site. Molecular dynamics simulations proved the stability of comp. 1/HSA complex. © 2014 by the authors.
T2  - ADMET and DMPK
T1  - Human Serum Albumin Binding of 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic Acid and its Mono-Me Esters
VL  - 2
IS  - 2
SP  - 126
EP  - 142
DO  - 10.5599/admet.2.2.28
ER  - 

@article{
author = "Cvijetić, Ilija and Petrović, D.D. and Verbić, Tatjana and Juranić, Ivan O. and Drakulić, B.J.",
year = "2014",
abstract = "Interactions of 2-[(carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic acid (compound 1) and its mono-Me ester (compound 2) with the human serum albumin (HSA) have been studied by fluorescence spectroscopy. Comp. 1 exerts antiproliferative activity toward human tumor cells and significant selectivity (tumor vs. healthy cells) in vitro. Competitive binding study with warfarin and ibuprofen as binding site probes, revealed that one molecule of comp. 1 selectively binds to HSA Sudlow site I (warfarin site) with moderate binding constant (Kb = (2.8 ± 0.5) × 104 M-1 at 37 ± 1 °C), while comp. 2 binds to Sudlow site II (Kb = (3.2 ± 0.9) × 104 M-1 at 37 ± 1 °C). Fluorescence quenching at different temperatures was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. Energy resonance transfer between HSA and comp. 1 was examined according to Förster's non-radiative energy transfer theory. Distance of about 10 Å between ligand and Trp214 (HSA) was obtained. Docking studies confirmed HSA Sudlow site I as a preferable comp. 1 binding site, and Sudlow site II as comp. 2 binding site. Molecular dynamics simulations proved the stability of comp. 1/HSA complex. © 2014 by the authors.",
journal = "ADMET and DMPK",
title = "Human Serum Albumin Binding of 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic Acid and its Mono-Me Esters",
volume = "2",
number = "2",
pages = "126-142",
doi = "10.5599/admet.2.2.28"
}

Cvijetić, I., Petrović, D.D., Verbić, T., Juranić, I. O.,& Drakulić, B.J.. (2014). Human Serum Albumin Binding of 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic Acid and its Mono-Me Esters. in ADMET and DMPK, 2(2), 126-142.
https://doi.org/10.5599/admet.2.2.28

Cvijetić I, Petrović D, Verbić T, Juranić IO, Drakulić B. Human Serum Albumin Binding of 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic Acid and its Mono-Me Esters. in ADMET and DMPK. 2014;2(2):126-142.
doi:10.5599/admet.2.2.28 .

Cvijetić, Ilija, Petrović, D.D., Verbić, Tatjana, Juranić, Ivan O., Drakulić, B.J., "Human Serum Albumin Binding of 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic Acid and its Mono-Me Esters" in ADMET and DMPK, 2, no. 2 (2014):126-142,
https://doi.org/10.5599/admet.2.2.28 . .

TY  - DATA
AU  - Tasić, Gordana
AU  - Ranđelović, Jelena
AU  - Vusurović, Nikola
AU  - Maslak, Veselin
AU  - Husinec, Suren
AU  - Savić, Vladimir
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3466
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Tetrahedron Letters
T1  - Supplementary data for article: Tasić, G.; Randjelovic, J.; Vusurovic, N.; Maslak, V.; Husinec, S.; Savić, V. A Highly Regioselective, Protecting Group Controlled, Synthesis of Bicyclic Compounds via Pd-Catalysed Intramolecular Cyclisations. Tetrahedron Letters 2013, 54 (18), 2243–2246. https://doi.org/10.1016/j.tetlet.2013.02.068
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3466
ER  - 

@misc{
author = "Tasić, Gordana and Ranđelović, Jelena and Vusurović, Nikola and Maslak, Veselin and Husinec, Suren and Savić, Vladimir",
year = "2013",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Tetrahedron Letters",
title = "Supplementary data for article: Tasić, G.; Randjelovic, J.; Vusurovic, N.; Maslak, V.; Husinec, S.; Savić, V. A Highly Regioselective, Protecting Group Controlled, Synthesis of Bicyclic Compounds via Pd-Catalysed Intramolecular Cyclisations. Tetrahedron Letters 2013, 54 (18), 2243–2246. https://doi.org/10.1016/j.tetlet.2013.02.068",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3466"
}

Tasić, G., Ranđelović, J., Vusurović, N., Maslak, V., Husinec, S.,& Savić, V.. (2013). Supplementary data for article: Tasić, G.; Randjelovic, J.; Vusurovic, N.; Maslak, V.; Husinec, S.; Savić, V. A Highly Regioselective, Protecting Group Controlled, Synthesis of Bicyclic Compounds via Pd-Catalysed Intramolecular Cyclisations. Tetrahedron Letters 2013, 54 (18), 2243–2246. https://doi.org/10.1016/j.tetlet.2013.02.068. in Tetrahedron Letters
Pergamon-Elsevier Science Ltd, Oxford..
https://hdl.handle.net/21.15107/rcub_cherry_3466

Tasić G, Ranđelović J, Vusurović N, Maslak V, Husinec S, Savić V. Supplementary data for article: Tasić, G.; Randjelovic, J.; Vusurovic, N.; Maslak, V.; Husinec, S.; Savić, V. A Highly Regioselective, Protecting Group Controlled, Synthesis of Bicyclic Compounds via Pd-Catalysed Intramolecular Cyclisations. Tetrahedron Letters 2013, 54 (18), 2243–2246. https://doi.org/10.1016/j.tetlet.2013.02.068. in Tetrahedron Letters. 2013;.
https://hdl.handle.net/21.15107/rcub_cherry_3466 .

Tasić, Gordana, Ranđelović, Jelena, Vusurović, Nikola, Maslak, Veselin, Husinec, Suren, Savić, Vladimir, "Supplementary data for article: Tasić, G.; Randjelovic, J.; Vusurovic, N.; Maslak, V.; Husinec, S.; Savić, V. A Highly Regioselective, Protecting Group Controlled, Synthesis of Bicyclic Compounds via Pd-Catalysed Intramolecular Cyclisations. Tetrahedron Letters 2013, 54 (18), 2243–2246. https://doi.org/10.1016/j.tetlet.2013.02.068" in Tetrahedron Letters (2013),
https://hdl.handle.net/21.15107/rcub_cherry_3466 .

TY  - DATA
AU  - Cvijetić, Ilija
AU  - Vitorović-Todorović, Maja D.
AU  - Juranić, Ivan O.
AU  - Drakulić, Branko J.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3515
PB  - Springer Wien, Wien
T2  - Monatshefte Fur Chemie
T1  - Supplementary data for article: Cvijetić, I.; Vitorović-Todorović, M. D.; Juranić, I. O.; Drakulić, B. J. Reactivity of (E)-4-Aryl-4-Oxo-2-Butenoic Acid Arylamides toward 2-Mercaptoethanol. A LFER Study. Monatshefte Fur Chemie 2013, 144 (12), 1815–1824. https://doi.org/10.1007/s00706-013-1084-6
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3515
ER  - 

@misc{
author = "Cvijetić, Ilija and Vitorović-Todorović, Maja D. and Juranić, Ivan O. and Drakulić, Branko J.",
year = "2013",
publisher = "Springer Wien, Wien",
journal = "Monatshefte Fur Chemie",
title = "Supplementary data for article: Cvijetić, I.; Vitorović-Todorović, M. D.; Juranić, I. O.; Drakulić, B. J. Reactivity of (E)-4-Aryl-4-Oxo-2-Butenoic Acid Arylamides toward 2-Mercaptoethanol. A LFER Study. Monatshefte Fur Chemie 2013, 144 (12), 1815–1824. https://doi.org/10.1007/s00706-013-1084-6",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3515"
}

Cvijetić, I., Vitorović-Todorović, M. D., Juranić, I. O.,& Drakulić, B. J.. (2013). Supplementary data for article: Cvijetić, I.; Vitorović-Todorović, M. D.; Juranić, I. O.; Drakulić, B. J. Reactivity of (E)-4-Aryl-4-Oxo-2-Butenoic Acid Arylamides toward 2-Mercaptoethanol. A LFER Study. Monatshefte Fur Chemie 2013, 144 (12), 1815–1824. https://doi.org/10.1007/s00706-013-1084-6. in Monatshefte Fur Chemie
Springer Wien, Wien..
https://hdl.handle.net/21.15107/rcub_cherry_3515

Cvijetić I, Vitorović-Todorović MD, Juranić IO, Drakulić BJ. Supplementary data for article: Cvijetić, I.; Vitorović-Todorović, M. D.; Juranić, I. O.; Drakulić, B. J. Reactivity of (E)-4-Aryl-4-Oxo-2-Butenoic Acid Arylamides toward 2-Mercaptoethanol. A LFER Study. Monatshefte Fur Chemie 2013, 144 (12), 1815–1824. https://doi.org/10.1007/s00706-013-1084-6. in Monatshefte Fur Chemie. 2013;.
https://hdl.handle.net/21.15107/rcub_cherry_3515 .

Cvijetić, Ilija, Vitorović-Todorović, Maja D., Juranić, Ivan O., Drakulić, Branko J., "Supplementary data for article: Cvijetić, I.; Vitorović-Todorović, M. D.; Juranić, I. O.; Drakulić, B. J. Reactivity of (E)-4-Aryl-4-Oxo-2-Butenoic Acid Arylamides toward 2-Mercaptoethanol. A LFER Study. Monatshefte Fur Chemie 2013, 144 (12), 1815–1824. https://doi.org/10.1007/s00706-013-1084-6" in Monatshefte Fur Chemie (2013),
https://hdl.handle.net/21.15107/rcub_cherry_3515 .

TY  - JOUR
AU  - Cvijetić, Ilija
AU  - Vitorović-Todorović, Maja D.
AU  - Juranić, Ivan O.
AU  - Drakulić, Branko J.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1441
AB  - The reactivity of fifteen (E)-4-aryl-4-oxo-2-butenoic (aroylacrylic) acid arylamides toward thiols was studied, measuring the rate constants of the addition of model thiol nucleophile, 2-mercaptoethanol. The influence of the variation of the substituents on the phenyl rings on the rate of reaction was quantified using the Hammett substituent constants and descriptors derived from ab initio or semiempirical calculations (atomic charges, HOMO, and LUMO). Statistically significant linear correlations between second-order rate constants and Hammett substituent constants, as well as energies of LUMO orbitals, were obtained. Substituents on both aroyl and arylamido moieties were shown to influence the reactivity of studied compounds toward thiols. The regioselectivity of reaction was confirmed by NMR spectroscopy. Exclusively beta-addition product with respect to the aroyl keto group was obtained. The determined enthalpy and entropy of activation were found to be in agreement with the proposed reaction mechanism, which includes a highly ordered transition state.
PB  - Springer Wien, Wien
T2  - Monatshefte Fur Chemie
T1  - Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study
VL  - 144
IS  - 12
SP  - 1815
EP  - 1824
DO  - 10.1007/s00706-013-1084-6
ER  - 

@article{
author = "Cvijetić, Ilija and Vitorović-Todorović, Maja D. and Juranić, Ivan O. and Drakulić, Branko J.",
year = "2013",
abstract = "The reactivity of fifteen (E)-4-aryl-4-oxo-2-butenoic (aroylacrylic) acid arylamides toward thiols was studied, measuring the rate constants of the addition of model thiol nucleophile, 2-mercaptoethanol. The influence of the variation of the substituents on the phenyl rings on the rate of reaction was quantified using the Hammett substituent constants and descriptors derived from ab initio or semiempirical calculations (atomic charges, HOMO, and LUMO). Statistically significant linear correlations between second-order rate constants and Hammett substituent constants, as well as energies of LUMO orbitals, were obtained. Substituents on both aroyl and arylamido moieties were shown to influence the reactivity of studied compounds toward thiols. The regioselectivity of reaction was confirmed by NMR spectroscopy. Exclusively beta-addition product with respect to the aroyl keto group was obtained. The determined enthalpy and entropy of activation were found to be in agreement with the proposed reaction mechanism, which includes a highly ordered transition state.",
publisher = "Springer Wien, Wien",
journal = "Monatshefte Fur Chemie",
title = "Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study",
volume = "144",
number = "12",
pages = "1815-1824",
doi = "10.1007/s00706-013-1084-6"
}

Cvijetić, I., Vitorović-Todorović, M. D., Juranić, I. O.,& Drakulić, B. J.. (2013). Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study. in Monatshefte Fur Chemie
Springer Wien, Wien., 144(12), 1815-1824.
https://doi.org/10.1007/s00706-013-1084-6

Cvijetić I, Vitorović-Todorović MD, Juranić IO, Drakulić BJ. Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study. in Monatshefte Fur Chemie. 2013;144(12):1815-1824.
doi:10.1007/s00706-013-1084-6 .

Cvijetić, Ilija, Vitorović-Todorović, Maja D., Juranić, Ivan O., Drakulić, Branko J., "Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study" in Monatshefte Fur Chemie, 144, no. 12 (2013):1815-1824,
https://doi.org/10.1007/s00706-013-1084-6 . .

TY  - JOUR
AU  - Tasić, Gordana
AU  - Ranđelović, Jelena
AU  - Vusurović, Nikola
AU  - Maslak, Veselin
AU  - Husinec, Suren
AU  - Savić, Vladimir
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1586
AB  - Intramolecular Pd-catalysed cyclisation reactions for the preparation of bicyclic compounds have been studied as a model system towards the synthesis of corialstonine and corialstonidine. Significant differences in reactivity have been observed for the cyclic allyl alcohols possessing O-protected and free OH functionalities. Cyclisation via the intramolecular Heck reaction, for both derivatives, proved to be highly regioselective and while the O-protected compound favoured the exo mode of cyclisation, the unprotected alcohol preferred the endo cyclisation pathway. Brief computational studies were carried out in order to obtain further insight into these processes.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Tetrahedron Letters
T1  - A highly regioselective, protecting group controlled, synthesis of bicyclic compounds via Pd-catalysed intramolecular cyclisations
VL  - 54
IS  - 18
SP  - 2243
EP  - 2246
DO  - 10.1016/j.tetlet.2013.02.068
ER  - 

@article{
author = "Tasić, Gordana and Ranđelović, Jelena and Vusurović, Nikola and Maslak, Veselin and Husinec, Suren and Savić, Vladimir",
year = "2013",
abstract = "Intramolecular Pd-catalysed cyclisation reactions for the preparation of bicyclic compounds have been studied as a model system towards the synthesis of corialstonine and corialstonidine. Significant differences in reactivity have been observed for the cyclic allyl alcohols possessing O-protected and free OH functionalities. Cyclisation via the intramolecular Heck reaction, for both derivatives, proved to be highly regioselective and while the O-protected compound favoured the exo mode of cyclisation, the unprotected alcohol preferred the endo cyclisation pathway. Brief computational studies were carried out in order to obtain further insight into these processes.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Tetrahedron Letters",
title = "A highly regioselective, protecting group controlled, synthesis of bicyclic compounds via Pd-catalysed intramolecular cyclisations",
volume = "54",
number = "18",
pages = "2243-2246",
doi = "10.1016/j.tetlet.2013.02.068"
}

Tasić, G., Ranđelović, J., Vusurović, N., Maslak, V., Husinec, S.,& Savić, V.. (2013). A highly regioselective, protecting group controlled, synthesis of bicyclic compounds via Pd-catalysed intramolecular cyclisations. in Tetrahedron Letters
Pergamon-Elsevier Science Ltd, Oxford., 54(18), 2243-2246.
https://doi.org/10.1016/j.tetlet.2013.02.068

Tasić G, Ranđelović J, Vusurović N, Maslak V, Husinec S, Savić V. A highly regioselective, protecting group controlled, synthesis of bicyclic compounds via Pd-catalysed intramolecular cyclisations. in Tetrahedron Letters. 2013;54(18):2243-2246.
doi:10.1016/j.tetlet.2013.02.068 .

Tasić, Gordana, Ranđelović, Jelena, Vusurović, Nikola, Maslak, Veselin, Husinec, Suren, Savić, Vladimir, "A highly regioselective, protecting group controlled, synthesis of bicyclic compounds via Pd-catalysed intramolecular cyclisations" in Tetrahedron Letters, 54, no. 18 (2013):2243-2246,
https://doi.org/10.1016/j.tetlet.2013.02.068 . .

TY  - DATA
AU  - Grozdanović, Milica M.
AU  - Drakulić, Branko J.
AU  - Gavrović-Jankulović, Marija
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3476
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Supplementary data for article: Grozdanovic, M. M.; Drakulić, B. J.; Gavrović-Jankulović, M. Conformational Mobility of Active and E-64-Inhibited Actinidin. Biochimica et Biophysica Acta: General Subjects 2013, 1830 (10), 4790–4799. https://doi.org/10.1016/j.bbagen.2013.06.015
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3476
ER  - 

@misc{
author = "Grozdanović, Milica M. and Drakulić, Branko J. and Gavrović-Jankulović, Marija",
year = "2013",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Supplementary data for article: Grozdanovic, M. M.; Drakulić, B. J.; Gavrović-Jankulović, M. Conformational Mobility of Active and E-64-Inhibited Actinidin. Biochimica et Biophysica Acta: General Subjects 2013, 1830 (10), 4790–4799. https://doi.org/10.1016/j.bbagen.2013.06.015",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3476"
}

Grozdanović, M. M., Drakulić, B. J.,& Gavrović-Jankulović, M.. (2013). Supplementary data for article: Grozdanovic, M. M.; Drakulić, B. J.; Gavrović-Jankulović, M. Conformational Mobility of Active and E-64-Inhibited Actinidin. Biochimica et Biophysica Acta: General Subjects 2013, 1830 (10), 4790–4799. https://doi.org/10.1016/j.bbagen.2013.06.015. in Biochimica et Biophysica Acta: General Subjects
Elsevier Science Bv, Amsterdam..
https://hdl.handle.net/21.15107/rcub_cherry_3476

Grozdanović MM, Drakulić BJ, Gavrović-Jankulović M. Supplementary data for article: Grozdanovic, M. M.; Drakulić, B. J.; Gavrović-Jankulović, M. Conformational Mobility of Active and E-64-Inhibited Actinidin. Biochimica et Biophysica Acta: General Subjects 2013, 1830 (10), 4790–4799. https://doi.org/10.1016/j.bbagen.2013.06.015. in Biochimica et Biophysica Acta: General Subjects. 2013;.
https://hdl.handle.net/21.15107/rcub_cherry_3476 .

Grozdanović, Milica M., Drakulić, Branko J., Gavrović-Jankulović, Marija, "Supplementary data for article: Grozdanovic, M. M.; Drakulić, B. J.; Gavrović-Jankulović, M. Conformational Mobility of Active and E-64-Inhibited Actinidin. Biochimica et Biophysica Acta: General Subjects 2013, 1830 (10), 4790–4799. https://doi.org/10.1016/j.bbagen.2013.06.015" in Biochimica et Biophysica Acta: General Subjects (2013),
https://hdl.handle.net/21.15107/rcub_cherry_3476 .

TY  - JOUR
AU  - Simic, Aleksandra Z.
AU  - Verbić, Tatjana
AU  - Sentić, Milica N.
AU  - Vojic, Mirjana P.
AU  - Juranić, Ivan O.
AU  - Manojlović, Dragan D.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1593
AB  - Ellagic acid is a biologically active polyphenol found in numerous fruits and vegetables. However, not many papers dealing with the electrochemical properties and protolytic equilibria of ellagic acid have been published so far. The electro-oxidation mechanism of ellagic acid was studied in methanol aqueous media (1:1, v/v) within the pH range of 1.5-9.0, t = 25 +/- A 1 A degrees C, using cyclic voltammetry on a glassy carbon electrode, and by semiempirical calculations. Results show that oxidation of ellagic acid is a pH-dependent, two-step quasireversible process. The slope of peak 1 indicates the exchange of the same number of electrons and protons within the whole studied pH range; the slope of peak 2 changes with the increase of pH, and three different regions are visible. As protolytic equilibria studies revealed that ellagic acid acts as a diprotic acid in the studied conditions (acidity constants were potentiometrically determined as pK (a1) = 5.42 +/- A 0.01 and pK (a2) = 6.76 +/- A 0.01), it is obvious that the electro-oxidation occurs at the hydroxyl group subjected to dissociation. The three different regions are therefore recognized as regions with different dominating species: unionized molecule (H(4)A), monoanion (H(3)A(-)), and dianion (H(2)A(2-)). UV/Vis spectral changes confirmed the proposed equilibria. Heat of formation and electron densities calculated at semiempirical level were used to propose the hydrogen and electron abstraction sites. According to the obtained results, a new mechanism of ellagic acid electro-oxidation is proposed.
PB  - Springer Wien, Wien
T2  - Monatshefte Fur Chemie
T1  - Study of ellagic acid electro-oxidation mechanism
VL  - 144
IS  - 2
SP  - 121
EP  - 128
DO  - 10.1007/s00706-012-0856-8
ER  - 

@article{
author = "Simic, Aleksandra Z. and Verbić, Tatjana and Sentić, Milica N. and Vojic, Mirjana P. and Juranić, Ivan O. and Manojlović, Dragan D.",
year = "2013",
abstract = "Ellagic acid is a biologically active polyphenol found in numerous fruits and vegetables. However, not many papers dealing with the electrochemical properties and protolytic equilibria of ellagic acid have been published so far. The electro-oxidation mechanism of ellagic acid was studied in methanol aqueous media (1:1, v/v) within the pH range of 1.5-9.0, t = 25 +/- A 1 A degrees C, using cyclic voltammetry on a glassy carbon electrode, and by semiempirical calculations. Results show that oxidation of ellagic acid is a pH-dependent, two-step quasireversible process. The slope of peak 1 indicates the exchange of the same number of electrons and protons within the whole studied pH range; the slope of peak 2 changes with the increase of pH, and three different regions are visible. As protolytic equilibria studies revealed that ellagic acid acts as a diprotic acid in the studied conditions (acidity constants were potentiometrically determined as pK (a1) = 5.42 +/- A 0.01 and pK (a2) = 6.76 +/- A 0.01), it is obvious that the electro-oxidation occurs at the hydroxyl group subjected to dissociation. The three different regions are therefore recognized as regions with different dominating species: unionized molecule (H(4)A), monoanion (H(3)A(-)), and dianion (H(2)A(2-)). UV/Vis spectral changes confirmed the proposed equilibria. Heat of formation and electron densities calculated at semiempirical level were used to propose the hydrogen and electron abstraction sites. According to the obtained results, a new mechanism of ellagic acid electro-oxidation is proposed.",
publisher = "Springer Wien, Wien",
journal = "Monatshefte Fur Chemie",
title = "Study of ellagic acid electro-oxidation mechanism",
volume = "144",
number = "2",
pages = "121-128",
doi = "10.1007/s00706-012-0856-8"
}

Simic, A. Z., Verbić, T., Sentić, M. N., Vojic, M. P., Juranić, I. O.,& Manojlović, D. D.. (2013). Study of ellagic acid electro-oxidation mechanism. in Monatshefte Fur Chemie
Springer Wien, Wien., 144(2), 121-128.
https://doi.org/10.1007/s00706-012-0856-8

Simic AZ, Verbić T, Sentić MN, Vojic MP, Juranić IO, Manojlović DD. Study of ellagic acid electro-oxidation mechanism. in Monatshefte Fur Chemie. 2013;144(2):121-128.
doi:10.1007/s00706-012-0856-8 .

Simic, Aleksandra Z., Verbić, Tatjana, Sentić, Milica N., Vojic, Mirjana P., Juranić, Ivan O., Manojlović, Dragan D., "Study of ellagic acid electro-oxidation mechanism" in Monatshefte Fur Chemie, 144, no. 2 (2013):121-128,
https://doi.org/10.1007/s00706-012-0856-8 . .

TY  - JOUR
AU  - Grozdanović, Milica M.
AU  - Drakulić, Branko J.
AU  - Gavrović-Jankulović, Marija
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1398
AB  - Background: Actinidin, a protease from kiwifruit, belongs to the C1 family of cysteine proteases. Cysteine proteases were found to be involved in many disease states and are valid therapeutic targets. Actinidin has a wide pH activity range and wide substrate specificity, which makes it a good model system for studying enzyme-substrate interactions. Methods: The influence of inhibitor (E-64) binding on the conformation of actinidin was examined by 2D PAGE, circular dichroism (CD) spectroscopy, hydrophobic ligand binding assay, and molecular dynamics simulations. Results: Significant differences were observed in electrophoretic mobility of proteolytically active and E-64-inhibited actinidin. CD spectrometry and hydrophobic ligand binding assay revealed a difference in conformation between active and inhibited actinidin. Molecular dynamics simulations showed that a loop defined by amino-acid residues 88-104 had greater conformational mobility in the inhibited enzyme than in the active one. During MD simulations, the covalently bound inhibitor was found to change its conformation from extended to folded, with the guanidino moiety approaching the carboxylate. Conclusions: Conformational mobility of actinidin changes upon binding of the inhibitor, leading to a sequence of events that enables water and ions to protrude into a newly formed cavity of the inhibited enzyme. Drastic conformational mobility of E-64, a common inhibitor of cysteine proteases found in many crystal structures stored in PDB, was also observed. General significance: The analysis of structural changes which occur upon binding of an inhibitor to a cysteine protease provides a valuable starting point for the future design of therapeutic agents.
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Conformational mobility of active and E-64-inhibited actinidin
VL  - 1830
IS  - 10
SP  - 4790
EP  - 4799
DO  - 10.1016/j.bbagen.2013.06.015
ER  - 

@article{
author = "Grozdanović, Milica M. and Drakulić, Branko J. and Gavrović-Jankulović, Marija",
year = "2013",
abstract = "Background: Actinidin, a protease from kiwifruit, belongs to the C1 family of cysteine proteases. Cysteine proteases were found to be involved in many disease states and are valid therapeutic targets. Actinidin has a wide pH activity range and wide substrate specificity, which makes it a good model system for studying enzyme-substrate interactions. Methods: The influence of inhibitor (E-64) binding on the conformation of actinidin was examined by 2D PAGE, circular dichroism (CD) spectroscopy, hydrophobic ligand binding assay, and molecular dynamics simulations. Results: Significant differences were observed in electrophoretic mobility of proteolytically active and E-64-inhibited actinidin. CD spectrometry and hydrophobic ligand binding assay revealed a difference in conformation between active and inhibited actinidin. Molecular dynamics simulations showed that a loop defined by amino-acid residues 88-104 had greater conformational mobility in the inhibited enzyme than in the active one. During MD simulations, the covalently bound inhibitor was found to change its conformation from extended to folded, with the guanidino moiety approaching the carboxylate. Conclusions: Conformational mobility of actinidin changes upon binding of the inhibitor, leading to a sequence of events that enables water and ions to protrude into a newly formed cavity of the inhibited enzyme. Drastic conformational mobility of E-64, a common inhibitor of cysteine proteases found in many crystal structures stored in PDB, was also observed. General significance: The analysis of structural changes which occur upon binding of an inhibitor to a cysteine protease provides a valuable starting point for the future design of therapeutic agents.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Conformational mobility of active and E-64-inhibited actinidin",
volume = "1830",
number = "10",
pages = "4790-4799",
doi = "10.1016/j.bbagen.2013.06.015"
}

Grozdanović, M. M., Drakulić, B. J.,& Gavrović-Jankulović, M.. (2013). Conformational mobility of active and E-64-inhibited actinidin. in Biochimica et Biophysica Acta: General Subjects
Elsevier Science Bv, Amsterdam., 1830(10), 4790-4799.
https://doi.org/10.1016/j.bbagen.2013.06.015

Grozdanović MM, Drakulić BJ, Gavrović-Jankulović M. Conformational mobility of active and E-64-inhibited actinidin. in Biochimica et Biophysica Acta: General Subjects. 2013;1830(10):4790-4799.
doi:10.1016/j.bbagen.2013.06.015 .

Grozdanović, Milica M., Drakulić, Branko J., Gavrović-Jankulović, Marija, "Conformational mobility of active and E-64-inhibited actinidin" in Biochimica et Biophysica Acta: General Subjects, 1830, no. 10 (2013):4790-4799,
https://doi.org/10.1016/j.bbagen.2013.06.015 . .

TY  - JOUR
AU  - Vitorović-Todorović, Maja D.
AU  - Cvijetić, Ilija
AU  - Juranić, Ivan O.
AU  - Drakulić, Branko J.
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1574
AB  - The 3D-QSAR analysis based on alignment independent descriptors (GRIND-2) was performed on the set of 110 structurally diverse, dual binding AChE reversible inhibitors. Three separate models were built, based on different conformations, generated following next criteria: (i) minimum energy conformations, (ii) conformation most similar to the co-crystalized ligand conformation, and (iii) docked conformation. We found that regardless on conformation used, all the three models had good statistic and predictivity. The models revealed the importance of protonated pyridine nitrogen of tacrine moiety for anti AChE activity, and recognized HBA and HBD interactions as highly important for the potency. This was revealed by the variables associated with protonated pyridinium nitrogen, and the two amino groups of the linker. MIFs calculated with the N1= (pyridinium nitrogen) and the DRY GRID probes in the AChE active site enabled us to establish the relationship between amino acid residues within AChE active site and the variables having high impact on models. External predictive power of the models was tested on the set of 40 AChE reversible inhibitors, most of them structurally different from the training set. Some of those compounds were tested on the different enzyme source. We found that external predictivity was highly sensitive on conformations used. Model based on docked conformations had superior predictive ability, emphasizing the need for the employment of conformations built by taking into account geometrical restrictions of AChE active site gorge. (C) 2012 Elsevier Inc. All rights reserved.
PB  - Elsevier Science Inc, New York
T2  - Journal of Molecular Graphics and Modelling
T1  - The 3D-QSAR study of 110 diverse, dual binding, acetylcholinesterase inhibitors based on alignment independent descriptors (GRIND-2). The effects of conformation on predictive power and interpretability of the models
VL  - 38
SP  - 194
EP  - 210
DO  - 10.1016/j.jmgm.2012.08.001
ER  - 

@article{
author = "Vitorović-Todorović, Maja D. and Cvijetić, Ilija and Juranić, Ivan O. and Drakulić, Branko J.",
year = "2012",
abstract = "The 3D-QSAR analysis based on alignment independent descriptors (GRIND-2) was performed on the set of 110 structurally diverse, dual binding AChE reversible inhibitors. Three separate models were built, based on different conformations, generated following next criteria: (i) minimum energy conformations, (ii) conformation most similar to the co-crystalized ligand conformation, and (iii) docked conformation. We found that regardless on conformation used, all the three models had good statistic and predictivity. The models revealed the importance of protonated pyridine nitrogen of tacrine moiety for anti AChE activity, and recognized HBA and HBD interactions as highly important for the potency. This was revealed by the variables associated with protonated pyridinium nitrogen, and the two amino groups of the linker. MIFs calculated with the N1= (pyridinium nitrogen) and the DRY GRID probes in the AChE active site enabled us to establish the relationship between amino acid residues within AChE active site and the variables having high impact on models. External predictive power of the models was tested on the set of 40 AChE reversible inhibitors, most of them structurally different from the training set. Some of those compounds were tested on the different enzyme source. We found that external predictivity was highly sensitive on conformations used. Model based on docked conformations had superior predictive ability, emphasizing the need for the employment of conformations built by taking into account geometrical restrictions of AChE active site gorge. (C) 2012 Elsevier Inc. All rights reserved.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Molecular Graphics and Modelling",
title = "The 3D-QSAR study of 110 diverse, dual binding, acetylcholinesterase inhibitors based on alignment independent descriptors (GRIND-2). The effects of conformation on predictive power and interpretability of the models",
volume = "38",
pages = "194-210",
doi = "10.1016/j.jmgm.2012.08.001"
}

Vitorović-Todorović, M. D., Cvijetić, I., Juranić, I. O.,& Drakulić, B. J.. (2012). The 3D-QSAR study of 110 diverse, dual binding, acetylcholinesterase inhibitors based on alignment independent descriptors (GRIND-2). The effects of conformation on predictive power and interpretability of the models. in Journal of Molecular Graphics and Modelling
Elsevier Science Inc, New York., 38, 194-210.
https://doi.org/10.1016/j.jmgm.2012.08.001

Vitorović-Todorović MD, Cvijetić I, Juranić IO, Drakulić BJ. The 3D-QSAR study of 110 diverse, dual binding, acetylcholinesterase inhibitors based on alignment independent descriptors (GRIND-2). The effects of conformation on predictive power and interpretability of the models. in Journal of Molecular Graphics and Modelling. 2012;38:194-210.
doi:10.1016/j.jmgm.2012.08.001 .

Vitorović-Todorović, Maja D., Cvijetić, Ilija, Juranić, Ivan O., Drakulić, Branko J., "The 3D-QSAR study of 110 diverse, dual binding, acetylcholinesterase inhibitors based on alignment independent descriptors (GRIND-2). The effects of conformation on predictive power and interpretability of the models" in Journal of Molecular Graphics and Modelling, 38 (2012):194-210,
https://doi.org/10.1016/j.jmgm.2012.08.001 . .